INHIBITION OF PAF-INDUCED GAS-EXCHANGE DEFECTS BY BETA-ADRENERGIC AGONISTS IN MILD ASTHMA IS NOT DUE TO BRONCHODILATION

Salbutamol inhibits neutropenia, increased airway resistance, and gas exchange abnormalities provoked by platelet-activating factor (PAF) ch allenge in normal persons. To further explore the intriguing dissociat ion between spirometric abnormalities and gas exchange defects shown i n patients with asthma, we investigated whether the salbutamol-induced improvement in gas exchange disturbances after PAF is the result of b ronchodilation by comparing this effect with that of ipratropium bromi de. We hypothesized that ipratropium bromide, an anticholinergic agent without vascular effects, should block PAF-induced bronchoconstrictio n but not interfere with its systemic, neutropenic, and gas exchange e ffects. We studied eight nonsmokers with mild asthma (26 +/- 2.0 SE yr of age) who, prior to PAF challenge (18 mu g), inhaled either ipratro pium bromide (80 mu g) or salbutamol (300 mu g) in a randomized, doubl e-blind, crossover fashion 1 wk apart. Peripheral blood neutrophils, r espiratory system resistance (Rrs), arterial blood gases and ventilati on-perfusion ((V)over dot A/(Q) over dot)) inequalities were measured 5, 15, and 45 min after PAF. Compared with pretreatment with salbutamo l, ipratropium bromide also blocked the increase of respiratory system resistance (Rrs) but did not prevent facial flushing and neutropenia (p < 0.03) at 5 min nor the decrease of Pa-O2 (p = 0.08 and 0.05), the increase of AaPO(2) (p < 0.02 each), and the deterioration of (V) ove r dot A/(Q) over dot relationships (p < 0.05 each) at 5 and 15 min, re spectively. This functional pattern was similar to that observed previ ously in normal subjects and in nonpremedicated asthmatic patients aft er PAF, with return to baseline values at 45 min. By contrast, salbuta mol blocked PAF-induced increased Rrs, in addition to all the other PA F-induced abnormalities. These findings indicate that, in patients wit h mild asthma, salbutamol inhibits PAF-induced neutropenia and gas exc hange abnormalities by mechanisms involving other than airway smooth m uscle narrowing, possibly by acting on both the bronchial and pulmonar y circulations.